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Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Objectives/Goals: Currently, a lack of screening markers and targeted therapies prevent clinicians from successfully treating PDAC. Precision medicine may allow oncologists to better combat this disease. To personalize care, knowledge of tumor protein posttranslational modifications, extracellular matrix makeup, and infiltrating immune cells is imperative. Methods/Study Population: Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was employed to characterize the N glycosylation state, the ECM composition, and immune cell populations present within 10 formalin fixed paraffin embedded PDAC patient samples. Molecular dry spray of PNGase F and Collagenase III followed by enzymatic digestion allowed for the release of N glycans and ECM peptides from the tissue. Multiplex immunohistochemistry with photocleavable, mass-tagged probes was also performed on each tissue. This analysis produced a spatial map of N glycans, ECM peptides and immune cells with their distribution and abundance color-coded as a heat map of each tissue. Results/Anticipated Results: This analysis produced a unique N-glycan signature associated with specific tumor regions (necrosis, invasive margin, etc.) and immune cell clusters. Additionally, immune cells within the PDAC tumor microenvironment were found to be organized into immature tertiary lymphoid structures composed primarily of CD20+ B cells. Finally, a distinct distribution of ECM peptides within and surrounding tumor tissue was visualized, and putative identifications have been assigned to these stromal elements. Discussion/Significance of Impact: In the future, insights from this hypothesis-generating study may be leveraged to identify diagnostic and prognostic biomarkers for PDAC to improve early diagnosis and treatment response rates. The N glycan signature, ECM composition, and immune activation state in liquid biopsies including serum and PBMCs will be compared to data from this study.
Sustained attention is integral to goal-directed tasks in everyday life. It is a demanding and effortful process prone to failure. Deficits are particularly prevalent in mood disorders. However, conventional methods of assessment, rooted in overall measures of performance, neglect the nuanced temporal dimensions inherent in sustained attention, necessitating alternative analytical approaches.
Methods
This study investigated sustained attention deficits and temporal patterns of attentional fluctuation in a large clinical cohort of patients with bipolar depression (BPd, n = 33), bipolar euthymia (BPe, n = 84), major depression (MDd, n = 38) and controls (HC, n = 138) using a continuous performance task (CPT). Longitudinal and spectral analyses were employed to examine trial-level reaction time (RT) data.
Results
Longitudinal analysis revealed a significant worsening of performance over time (vigilance decrement) in BPd, whilst spectral analysis unveiled attentional fluctuations concentrated in the frequency range of 0.077 Hz (1/12.90 s)–0.049 Hz (1/20.24 s), with BPd and MDd demonstrating greater spectral power compared to BPe and controls.
Conclusions
Although speculative, the increased variability in this frequency range may have an association with the dysfunctional activity of the Default Mode Network, which has been shown to oscillate at a similar timescale. These findings underscore the importance of considering the temporal dimensions of sustained attention and show the potential of spectral analysis of RT in future clinical research.
A review of the existing techniques for the analysis of three-way data revealed that none were appropriate to the wide variety of data usually encountered in psychological research, and few were capable of both isolating common information and systematically describing individual differences. An alternating least squares algorithm was proposed to fit both an individual difference model and a replications component model to three-way data which may be defined at the nominal, ordinal, interval, ratio, or mixed measurement level; which may be discrete or continuous; and which may be unconditional, matrix conditional, or row conditional. This algorithm was evaluated by a Monte Carlo study. Recovery of the original information was excellent when the correct measurement characteristics were assumed. Furthermore, the algorithm was robust to the presence of random error. In addition, the algorithm was used to fit the individual difference model to a real, binary, subject conditional data set. The findings from this application were consistent with previous research in the area of implicit personality theory and uncovered interesting systematic individual differences in the perception of political figures and roles.
Russia's invasion of Ukraine has pushed Europe into a new strategic era. The knock-on effects of the war have combined to open a period of reordering across the European continent. European governments and the European Union collectively have begun to fashion policies for this shift, recognizing this to be a pivotal historical moment.
Richard Youngs unpacks the different dynamics that have come to characterize European policies in the wake of the war: the nature of EU integration, geopolitical power, defence priorities, European borders, liberal values, the green transition and economic sovereignty. The book looks to the future and outlines the issues and choices with which European governments still need to grapple. Youngs develops the notion of geoliberalism as a way of addressing these challenges and guiding European governments and the EU into the fragile order taking shape in the shadow of Ukraine's war.
Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
The preceding chapters have attempted to look beyond the immediate fog of war and reflect upon the longer-term impacts of Ukraine's conflict. The war presents a range of profound questions that flow from these aftershocks. Although it is clear that the conflict is set to have lasting effects on Europe, two years on from Russia's invasion it remains uncertain how much structural re-ordering it will entail and what kinds of change will ultimately prevail. Will the emerging European order ultimately be a more harmonious and values-based one, or the reflection of greater turmoil and nationally centred self-preservation? Will European peace and liberal values ultimately emerge from the tragedy re-empowered? Or does the conflict mark another step in inexorable Western decline and solipsistic fragmentation? Will Russia's influence now be excised from the wider European order, or is it set to become even more disruptive?
These are the kinds of questions that will feature prominently in European affairs in the years to come. European governments are beginning to map out their responses, but do not yet have a clear, long-term plan for the kind of European order best able to advance regional peace and prosperity. It is undoubtedly the case that the conflict has spurred an unprecedented range and depth of policy change; how much deep re-ordering this generates is more difficult to determine. While the war is ongoing and these issues are still very much in flux, however, it is possible to draw reflections that can help guide thinking about the emerging postwar European order.
PARTIAL RE-ORDERING
Much of the debate about European responses to the war has been about very specific and immediate imperatives of supporting Ukraine. However, it has also involved some signs that point towards deeper re-ordering – at least potentially. European governments have come to reconsider some of the core concepts or principles that have nominally been central to their long-standing notions of order. The emergent tenets touch upon some core structural parameters of the way that the European order is organized internally and also how it stands in relation to its immediate borderlands and other powers. The book has ranged widely over different areas of policy and institutional restructuring precisely because this breadth of change shows that the war has had multiple layers of impact, and it is this very multiplicity that amounts to the stirrings of a potential re-ordering that extends beyond modifications to individual policies only.
One of the clearest and most frequently commented effects of the Russian invasion is that European governments have developed stronger defence and security policies. They have reacted to the evident threat coming directly from Russia as well as to a wider sense of risk and uncertainty. The war has triggered a process of European rearmament, after years in which the continent was losing hard power relative to other countries. NATO has returned to the forefront of regional security and the EU has accelerated its complementary contributions to strengthening defence capabilities. Much day-to-day debate has focused on European governments’ military supplies to Ukrainian forces, these expanding as the conflict has continued.
These changes mean that the postwar order is becoming a more securitized one. It will no longer be rooted in a peace project that minimizes military power as was the case during decades of European cooperative identity-building. The fusion of hard, geopolitical power with the maintenance of liberal order is one key element of an emerging geoliberal Europe. Still, there are unresolved questions about the political implications of such securitization and what it implies for European perspectives on postwar re-ordering. For now, European governments have begun a process of rearmament without a template for dovetailing such securitization with other pillars of European order.
DEFENDING EUROPE
In the wake of the war, European governments have poured huge amounts of money into their defence budgets and have cooperated in developing new military technology. Gone are the celebrated days of a non-military, civilian power Europe. The EU has doubled down on defending and protecting its own perimeter. Elements of hard security have crept into key areas of its external actions. Here, NATO has played lead role: a striking result of the war is that this organization has returned to the forefront of European order. A common argument is that continental rearmament is a necessary and overdue step towards European governments giving concrete backing to their new language of power and pursuing a properly robust sovereignty to underpin liberal order in Europe.
The move towards rearming Europe began very tentatively in the two or three years before the war. The economic impact of the eurozone crisis had caused many governments to reduce defence spending dramatically after 2009 and for most of the 2010s European military spending flatlined, while it increased fast in China, Russia and the Middle East.
Alongside their primary focus on security and power politics, European governments have cast the war on Ukraine as a battle for liberal democratic values. The war has heightened concerns over the need to defend democracy and a belated recognition that stronger commitment is needed to halt an advance of authoritarianism. While many threats to democratic norms deepened in the years before 2022, the war has brought support for democracy and re-ordering more closely together as two sides of the same strategic coin. Part of the geoliberal Europe emerging in the war's shadow lies in the geopolitical importance of liberal democracy. Russia's attack so brutally shows the ills of authoritarianism that it has to some extent revitalized European governments’ support for democracy and the demand for such support from democratic reformers.
There are three circles or layers of this enhanced effort to deepen and protect democratic values: inside the European Union, in the countries of the wider European order, and at the global level. In each of these spheres, European governments and the EU have stepped up important elements of their democracy strategies. Yet, some tensions have also sharpened between the security and democracy components of European policies. A serious challenge is that the postwar drive towards securitization and alliance-building in places cuts across governments’ actions in favour of democracy. These security strands of European re-ordering sit uneasily with the promise of renewed liberal power, and they muddy the clarity of a democratic geoliberalism.
DEMOCRACY AND EUROPEAN ORDER
During the crisis-blighted years of the 2010s, the quality of European democracy suffered. National governments and the EU institutions did a poor job in upholding core democratic values. Rather than steadfastly defending democracy, most governments across the continent chipped away at civic space and independent checks and balances. Governments were slow in recognizing the risk that the digital sphere and tech companies represented to democracy. The EU failed to respond in any effective manner to democratic backsliding, most notably in Hungary and Poland, but in other states too. And it failed to offer much concrete support to activists as these sought new forms of democratic renewal across Europe. Many of the EU crisis measures implemented during the eurozone crisis were imposed with little accountability or popular debate and made the democratic malaise worse. Outside the union, the UK's post-Brexit democracy suffered turmoil and illiberal constriction.
As a corollary to rearmament, the war on Ukraine has begun to change the political geography of European order. It has opened a process of what can be termed “re-bordering”, as governments change the ways in which they establish boundaries to the European order. This process is remoulding the logics of inclusion in and exclusion from that order. For many years, the European Union has used strategically creative ambiguity in its boundary drawing and tried to avoid defining the logics of inclusion and exclusion in an absolute fashion. Throughout the 2010s, it denied formal inclusion to Ukraine and other Eastern European states and yet brought them closer to many parts of the EU institutional framework. Conversely, it avoided a complete breach with Russia even as tensions accumulated after the annexation of Crimea.
Since Russia's full invasion of Ukraine in February 2022, European powers have begun to draw boundary divisions in a much sharper fashion. The blurring between inclusion and exclusion has given way to what could become a much more definite logic of hard bordering. On one side of this equation, the EU has opened the possibility of Ukraine, Moldova and Georgia joining the union, moving them from a grey-zone buffer towards full inclusion in the core European order (examined in Chapter 6). On the other side of the equation, a more absolute divide has opened between the core European order and Russia, and this is integral to the emergent geoliberal Europe.
The step-by-step distancing between EU and other European powers, on the one side, and Russia, on the other side, has been one of the most obvious and exhaustively commented results of the war. The logic of exclusion is not absolute: many in Europe still resist the idea of re-ordering being intrinsically a process against Russia, seeing it rather as a less absolute turn away from Russia that might still be undone. And there are other complex nuances at play too, to do with the lack of exclusionary demarcations internationally, notions of a Russia-led competing order and also the societal dimensions of relations with Russia. Still, with these caveats, it can be said that the intersection between European order and the logic of exclusion towards Russia is now a powerful driver of continental geopolitics.
A final part of the re-ordering puzzle relates to the war's impact on European conceptions of economic order. Although this is an indirect impact and not so central to the conflict as the matters covered by other chapters, it is still significant in its importance and worthy of examination. The war has reinforced concerns about changes to economic order that have become prominent over the past several years. The fact that it has impacted the economic realm and not just issues related directly to security shows how deep the process of European re-ordering could extend. In effect, two order-related challenges have intensified together: a politico-security one in Europe, and a geoeconomic one within the wider international economic order. While this book is not concerned with economic or trade policy as such, these areas condition the link between the conflict and the core issue of European order.
The war has added dramatically to the priority that European governments attach to economic security. The postwar European order will be one that is rooted in different forms of economic order, interdependence and geoeconomics. The emergence of a geoliberal Europe can be seen in European powers adopting an increasingly political approach to their economic interests and leverage. This shift brings the foundations of economic order more into line with mounting uncertainties that beset geopolitical order. However, at least some European economic policies still tilt towards a narrow or defensive mercantilism that does not serve a systemic and balanced geoliberal approach to postwar re-ordering. The heightened priority now given to economic sovereignty is both an important pillar of geoliberal Europe and a potential challenge to fully strategic geoliberalism.
COMPETITIVE GLOBALISM
In the several years before the war, the EU had already been shifting to a more mercantile external economic strategy – driven in particular by Chinese commercial dominance. The Covid-19 pandemic triggered a raft of initiatives aimed to reduce European dependencies on global supply chains. The significance of the Ukraine war is that it has magnified these prior policy concerns and has become entangled with a much wider range of underlying geoeconomic patterns of re-ordering.
In the decade prior to Russia's full-scale invasion of Ukraine in early 2022, the EU had gradually adopted a more controlled and strategically transactional model of economic order. After the financial and economic crisis hit Europe from 2009, the EU more tightly conditioned other powers’ access to European markets.